Solid lipid nanoparticles (SLNs) are for example used as a novel approach for oral as well as for parenteral lipophilic or amphiphilic active ingredients delivery. Today the most common way for such delivery are emulsions.
SLN are suitable for such a use due to several important advantages such as                (i) incorporation of lipophilic as well as amphiphilic active ingredients, and        (ii) no biotoxicity, and        (iii) avoidance of organic solvents, and        (iv) possibility of controlled active ingredients release, and        (v) excellent stability (mechanical and chemical), and        (vi) usable for spray-drying, and        (vii) good optical properties (allows the production of non-turbid formulations), and        (viii) sterilisable.        
SLNs have a (more or less) spherical shape with a diameter of 10-1000 nm. In case non-turbid formulation are to be produced, then the diameter of the SLNs should be between 50-300 nm.
SLNs possess a solid lipid core which is stabilized by emulsifiers.
SLNs are known from the prior art such as Mehnert et al., Adv. Drug Del. Rev. 47 (2001), 165-196.
The lipid phase (lipid core) of the SLN is in a solid state (aka crystallized). This phase may comprise lipophilic and/or amphiphilic active ingredients (such as antimicrobial, antioxidants, polyphenols, vitamins, poly unsaturated fatty acids (PUFAs), dyestuffs, etc), which are (if they are included in the solid state) protected from degradation.
This is a very important further advantage which allows to prolonging the shelf life of lipophilic or amphiphilic active ingredients in a sophisticated way.
Crystallized lipids can form usually three different kinds of crystals:
α, β′, and β crystals.
The α-crystal chains have hexagonal arrangement, with the shortest spacing line in X-ray diffraction pattern. Furthermore, this crystal type has the least densely packed lipid structure and it melts at temperatures below that of the other crystals.
The β′-crystals are the transition form between α- and β-crystals, and they are orthorhombic. They are more ordered than α-crystals and melt at higher temperatures.
The β-crystals are packed in triclinic arrangement and have highly ordered platelet-like structures. They are the most stable form, and therefore they melt at the highest temperature. Due to kinetic reasons the crystals rearrange themselves from less ordered α-crystals to highly ordered β-crystals implying a shape change from spherical to plated shaped particles (Bunjes, Steiniger, & Richter, 2007). From this it follows, that the oil-water surface area increases leading to aggregation and gel formation of hydrophobic patches.
But in order to include a bioactive ingredient into the lipid core of the SLN, without incurring the above mentioned phase separation the unstable α and/or β′-crystal structure is preferred.
The goal of the present invention is to find a way to provide SLN with a α and/or β′-crystal structure which is stable and therefore does not polymorph into the β crystal structure. The SLN must be (storage) stable for weeks.
Surprisingly, it was found that when a specific emulsifier was used (which is at least one saponin), then a stable SLN wherein the solid lipid has a α and/or β′-crystal structure is obtained.
Therefore the present invention relates to solid lipid nanoparticles (I) comprising                (a) a core comprising                    (i) a lipid phase in a solid state, and            (ii) optionally at least one lipophilic and/or amphiphilic active ingredient, and                        (b) an emulsifier system comprising                    (i) at least one emulsifiercharacterised inthat the emulsifier system comprises at least one saponin.                        
Furthermore it is preferred that the emulsifier system of the SLN has a crystallization point which is lower than the crystallization point of the core of the SLN. That means that the emulsifier system should crystallize before the core crystallizes.
Therefore the present invention also relates to solid lipid nanoparticles (II), which are solid lipid nanoparticles (I), wherein the emulsifier system has a crystallization point which is lower than the crystallization point of the core.
The lipid phase can be any oil (mixture of oils), which is solid at the storage temperature of the SLN. Suitable oils are for example triglycerides, partial glycerides, fatty acids, steroids and waxes.
Therefore the present invention also relates to solid lipid nanoparticles (III), which are solid lipid nanoparticles (I) or (II), wherein the lipid phase is an oil (mixture of oils), which is solid at the storage temperature of the SLN. Suitable oils are for example triglycerides, partial glycerides, fatty acids, steroids and waxes.
Therefore the present invention also relates to solid lipid nanoparticles (III′), which are solid lipid nanoparticles (I), (II) or (III), wherein the lipid phase is an oil (mixture of oils) chosen from the group consisting of triglycerides, partial glycerides, fatty acids, steroids and waxes.
The lipophilic and/or amphiphilic active ingredient can be for example an antimicrobial, an antioxidant, a polyphenol, a vitamin, a PUFA or a dyestuff, as well as mixtures of such ingredients.
Therefore the present invention also relates to solid lipid nanoparticles (IV), which are solid lipid nanoparticles (I), (II), (III) or (III′), wherein the lipophilic and/or amphiphilic active ingredient is chosen from the group consisting of antimicrobial, an antioxidant, a polyphenol, a vitamin, a PUFA or a dyestuff, as well as mixtures of such ingredients.